Cluster headache and kynurenines
Abstract Background The glutamatergic neurotransmission has important role in the pathomechanism of primary headache disorders. The kynurenine metabolites derived from catabolism of tryptophan (Trp) have significant involvement not only in glutamatergic processes, but also in the neuroinflammation,...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | The Journal of Headache and Pain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10194-023-01570-9 |
| _version_ | 1797849915085291520 |
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| author | Bernadett Tuka Tamás Körtési Nikolett Nánási Ferenc Tömösi Tamás Janáky Dániel Veréb Délia Szok János Tajti László Vécsei |
| author_facet | Bernadett Tuka Tamás Körtési Nikolett Nánási Ferenc Tömösi Tamás Janáky Dániel Veréb Délia Szok János Tajti László Vécsei |
| author_sort | Bernadett Tuka |
| collection | DOAJ |
| description | Abstract Background The glutamatergic neurotransmission has important role in the pathomechanism of primary headache disorders. The kynurenine metabolites derived from catabolism of tryptophan (Trp) have significant involvement not only in glutamatergic processes, but also in the neuroinflammation, the oxidative stress and the mitochondrial dysfunctions. Previously we identified a depressed peripheral Trp metabolism in interictal period of episodic migraineurs, which prompted us to examine this pathway in patients with episodic cluster headache (CH) as well. Our aims were to compare the concentrations of compounds both in headache-free and attack periods, and to find correlations between Trp metabolism and the clinical features of CH. Levels of 11 molecules were determined in peripheral blood plasma of healthy controls (n = 22) and interbout/ictal periods of CH patients (n = 24) by neurochemical measurements. Findings Significantly decreased L-kynurenine (KYN, p < 0.01), while increased quinolinic acid (QUINA, p < 0.005) plasma concentrations were detected in the interbout period of CH patients compared to healthy subjects. The levels of KYN are further reduced during the ictal period compared to the controls (p < 0.006). There was a moderate, negative correlation between disease duration and interbout QUINA levels (p < 0.048, R = − 0.459); and between the total number of CH attacks experienced during the lifetime of patients and the interbout KYN concentrations (p < 0.024, R = − 0.516). Linear regression models revealed negative associations between age and levels of Trp, kynurenic acid, 3-hdyroxyanthranilic acid and QUINA in healthy control subjects, as well as between age and ictal level of anthranilic acid. Conclusions Our results refer to a specifically altered Trp metabolism in CH patients. The onset of metabolic imbalance can be attributed to the interbout period, where the decreased KYN level is unable to perform its protective functions, while the concentration of QUINA, as a toxic compound, increases. These processes can trigger CH attacks, which may be associated with glutamate excess induced neurotoxicity, neuroinflammation and oxidative stress. Further studies are needed to elucidate the exact functions of these molecular alterations that can contribute to identify new, potential biomarkers in the therapy of CH. |
| first_indexed | 2024-04-09T18:52:57Z |
| format | Article |
| id | doaj.art-98904679be004e20b1d831426f210864 |
| institution | Directory Open Access Journal |
| issn | 1129-2377 |
| language | English |
| last_indexed | 2024-04-09T18:52:57Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj.art-98904679be004e20b1d831426f2108642023-04-09T11:22:45ZengBMCThe Journal of Headache and Pain1129-23772023-04-0124111110.1186/s10194-023-01570-9Cluster headache and kynureninesBernadett Tuka0Tamás Körtési1Nikolett Nánási2Ferenc Tömösi3Tamás Janáky4Dániel Veréb5Délia Szok6János Tajti7László Vécsei8ELKH-SZTE Neuroscience Research Group, Department of Neurology, Faculty of Medicine, University of SzegedELKH-SZTE Neuroscience Research Group, Department of Neurology, Faculty of Medicine, University of SzegedELKH-SZTE Neuroscience Research Group, Department of Neurology, Faculty of Medicine, University of SzegedDepartment of Medical Chemistry, Interdisciplinary Excellence Centre, University of SzegedDepartment of Medical Chemistry, Interdisciplinary Excellence Centre, University of SzegedDepartment of Radiology, Faculty of Medicine, University of SzegedDepartment of Neurology, Albert Szent-Györgyi Medical School, University of SzegedDepartment of Neurology, Albert Szent-Györgyi Medical School, University of SzegedELKH-SZTE Neuroscience Research Group, Department of Neurology, Faculty of Medicine, University of SzegedAbstract Background The glutamatergic neurotransmission has important role in the pathomechanism of primary headache disorders. The kynurenine metabolites derived from catabolism of tryptophan (Trp) have significant involvement not only in glutamatergic processes, but also in the neuroinflammation, the oxidative stress and the mitochondrial dysfunctions. Previously we identified a depressed peripheral Trp metabolism in interictal period of episodic migraineurs, which prompted us to examine this pathway in patients with episodic cluster headache (CH) as well. Our aims were to compare the concentrations of compounds both in headache-free and attack periods, and to find correlations between Trp metabolism and the clinical features of CH. Levels of 11 molecules were determined in peripheral blood plasma of healthy controls (n = 22) and interbout/ictal periods of CH patients (n = 24) by neurochemical measurements. Findings Significantly decreased L-kynurenine (KYN, p < 0.01), while increased quinolinic acid (QUINA, p < 0.005) plasma concentrations were detected in the interbout period of CH patients compared to healthy subjects. The levels of KYN are further reduced during the ictal period compared to the controls (p < 0.006). There was a moderate, negative correlation between disease duration and interbout QUINA levels (p < 0.048, R = − 0.459); and between the total number of CH attacks experienced during the lifetime of patients and the interbout KYN concentrations (p < 0.024, R = − 0.516). Linear regression models revealed negative associations between age and levels of Trp, kynurenic acid, 3-hdyroxyanthranilic acid and QUINA in healthy control subjects, as well as between age and ictal level of anthranilic acid. Conclusions Our results refer to a specifically altered Trp metabolism in CH patients. The onset of metabolic imbalance can be attributed to the interbout period, where the decreased KYN level is unable to perform its protective functions, while the concentration of QUINA, as a toxic compound, increases. These processes can trigger CH attacks, which may be associated with glutamate excess induced neurotoxicity, neuroinflammation and oxidative stress. Further studies are needed to elucidate the exact functions of these molecular alterations that can contribute to identify new, potential biomarkers in the therapy of CH.https://doi.org/10.1186/s10194-023-01570-9Episodic cluster headacheInterbout and ictal periodsPlasma kynurenine metabolitesClinical features |
| spellingShingle | Bernadett Tuka Tamás Körtési Nikolett Nánási Ferenc Tömösi Tamás Janáky Dániel Veréb Délia Szok János Tajti László Vécsei Cluster headache and kynurenines The Journal of Headache and Pain Episodic cluster headache Interbout and ictal periods Plasma kynurenine metabolites Clinical features |
| title | Cluster headache and kynurenines |
| title_full | Cluster headache and kynurenines |
| title_fullStr | Cluster headache and kynurenines |
| title_full_unstemmed | Cluster headache and kynurenines |
| title_short | Cluster headache and kynurenines |
| title_sort | cluster headache and kynurenines |
| topic | Episodic cluster headache Interbout and ictal periods Plasma kynurenine metabolites Clinical features |
| url | https://doi.org/10.1186/s10194-023-01570-9 |
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